Cell fusion in osteoclasts plays a critical role in controlling bone mass and osteoblastic activity.
The balance between osteoclast and osteoblast activity is central for maintaining the integrity of bone homeostasis. Here we show that mice lacking dendritic cell specific transmembrane protein (DC-STAMP), an essential molecule for osteoclast cell-cell fusion, exhibited impaired bone resorption and upregulation of bone formation by osteoblasts, which do not express DC-STAMP, which led to increased bone mass. On the contrary, DC-STAMP over-expressing transgenic (DC-STAMP-Tg) mice under the control of an actin promoter showed significantly accelerated cell-cell fusion of osteoclasts and bone resorption, with decreased osteoblastic activity and bone mass. Bone resorption and formation are known to be regulated in a coupled manner, whereas DC-STAMP regulates bone homeostasis in an un-coupled manner. Thus our results indicate that inhibition of a single molecule provides both decreased osteoclast activity and increased bone formation by osteoblasts, thereby increasing bone mass in an un-coupled and a tissue specific manner.
Iwasaki
Ryotaro
R
Department of Cell Differentiation, The Sakaguchi Laboratory of Developmental Biology, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8582, Japan.
Ninomiya
Ken
K
Miyamoto
Kana
K
Suzuki
Toru
T
Sato
Yuiko
Y
Kawana
Hiromasa
H
Nakagawa
Taneaki
T
Suda
Toshio
T
Miyamoto
Takeshi
T
D000199:Actins / Q000235:genetics; D000818:Animals; D015519:Bone Density / Q000235:genetics; D002459:Cell Fusion; D006706:Homeostasis; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D010006:Osteoblasts / Q000166:cytology / Q000502:physiology*; D010010:Osteoclasts / Q000166:cytology / Q000502:physiology*; D010012:Osteogenesis / Q000235:genetics / Q000502:physiology*; D011401:Promoter Regions, Genetic; D053245:RANK Ligand / Q000494:pharmacology
D000199:Actins; C499636:DC-STAMP protein, mouse; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D053245:RANK Ligand; C505689:Tnfsf11 protein, mouse